A major objective this year will be to evaluate orthoiodo sodium benzoate (OISB), a chemical agent that can increase oxyhemoglobin dissociation 3-4 times more than nitroglycerin in vivo. We will then determine if the hypoxic myocardium can utilize the oxygen made available when OISB or nitroglycerin increases the P-50 value of blood in vivo. We will determine if the induction of myocardial hypoxia in the isolated supported dog heart preparation can produce a spontaneous increase in coronary venous P-50 values. A positive finding would suggest that hypoxia per se might liberate an endogenous substance from the myocardium that increases coronary venous P-50. The decrease in MVO2 induced by nitroglycerin and adenosine will be evaluated to determine if this effect has a metabolic basis and reflects changes in substrate utilization by the myocardium. Studies on regional myocardial blood flow will be extended to include the intact dog heart in which a flow limiting stenosis will be introduced into a single major coronary artery. The effect of this stenosis on the epicardial/endocardial transmural blood flow distribution will be analyzed in a manner similar to our previous studies in the isolated supported heart preparation.